Jingjie Wang

Downregulation of microRNA-206 is a potent prognostic marker for patients with gastric cancer.

Background MicroRNA-206 (miR-206), as a homolog of miR-1, plays important roles in tumorigenesis and tumor progression of various human malignancies, including breast cancer, endometrial endometrioid carcinoma, rhabdomyosarcoma, glioma, lung cancer, and laryngeal cancer. However, its involvement in gastric cancer has remained unclear. Aim To examine the expression patterns and clinical implications of miR-206 in gastric cancer. Materials and methods Quantitative RT-PCR was performed to evaluate the expression levels of miR-206 in 98 pairs of gastric cancer and normal adjacent mucosa. In addition, the clinicopathologic significance and the prognostic value of miR-206 expression were further determined. Results At first, miR-206 expression was significantly downregulated in gastric cancer tissues when compared with normal adjacent mucosa (P<0.001). Next, tumors with low miR-206 expression had a greater extent of lymph node metastasis (P=0.01), presence of venous invasion (P=0.008), and hematogenous recurrence (P=0.01), and were at a worse stage (P=0.03) than the tumors with a high miR-206 expression. Then, the gastric cancer patients with a low miR-206 expression had shorter overall survival than those with a high miR-206 expression (P=0.02). Furthermore, multivariate analysis showed that miR-206 expression was an independent prognostic factor for patients with gastric cancer. Conclusion Our results strongly suggest that the downregulation of miR-206 was significantly correlated with tumor progression and may be a potent prognostic marker of gastric cancer. miR-206 might serve as a promising therapeutic target for the treatment of this cancer.

Curcumin attenuates insulin resistance in hepatocytes by inducing Nrf2 nuclear translocation.

BACKGROUND/AIMS NF-E2-Related Factor-2 (Nrf2) is a transcription factor that plays a crucial role in the cellular protection against oxidative stress. Curcumin has been reported to induce Nrf2 nuclear translocation and upregulate the expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes in hepatocytes. This study was designed to investigate whether curcumin-induced Nrf2 nuclear translocation could reduce ROS-mediated insulin resistance in cultured LO2 hepatocytes. METHODOLOGY Human LO2 hepatocytes were incubated with curcumine and glucose oxidase (GO) in the presence/absence of wortmannin (a phosphatidyinositol 3-kinase (PI3K) inhibitor), oxidative stress, cellular damage, Nrf2 nuclear translocation and insulin resistance were measured. RESULTS GO exposure significantly increased intracellular ROS, glutathione (GSH) depletion, malondialdehyde (MDA) formation, and increased activities of cellular lactate dehydrogenase (LDH) and aspartate amino transferase (AST), as well as causing insulin resistance. Curcumin pretreatment significantly attenuated these disturbances in intracellular ROS, liver enzyme activity and significantly antagonized the lipid peroxidation, GSH depletion and insulin resistance induced by GO in LO2 hepatocytes. These effects paralleled Nrf2 nuclear translocation induced by curcumin. Wortmannin partially blocked curcumin-induced Nrf2 nuclear translocation. In addition, wortmannin prevented curcumin-induced improvements in intracellular ROS, MDA formation, GSH depletion, liver enzyme activity and insulin resistance in cultured LO2 hepatocytes. CONCLUSIONS These findings suggest that curcumin could reduce ROS-mediated insulin resistance in hepatocytes, at least in part through nuclear translocation of Nrf2.

Curcumin upregulates Nrf2 nuclear translocation and protects rat hepatic stellate cells against oxidative stress.

The present study aimed to investigate the protective role of curcumin against oxidative stress in rat hepatic stellate cells (HSCs)-T6, and to determine the possible underlying mechanisms. HSC-T6 cells were divided into three groups: Negative control group, oxidant-treated group and curcumin-treated group. Flow cytometry and spectrophotometry were used to measure the production of reactive oxygen species (ROS), and the levels of malondialdehyde (MDA) and glutathione (GSH). Immunocytochemistry and a radioimmunoassay were used to determine the expression of smooth muscle α-actin (α-SMA) and the secretion of extracellular matrix (ECM) molecules. In addition, western blotting and immunocytochemistry were used to determine the expression levels of nuclear factor-erythroid 2-related factor (Nrf2). Treatment with glucose oxidase (GO) significantly stimulated the formation of ROS and increased the production of MDA, as compared with the control cells; however, the production of GSH was only slightly increased. In addition, treatment with GO significantly promoted the expression of α-SMA and the secretion of ECM molecules. Conversely, treatment with curcumin significantly decreased the levels of ROS and MDA, and significantly increased the levels of GSH. Curcumin significantly inhibited the expression of α-SMA and decreased the secretion of ECM molecules. Furthermore, treatment with curcumin significantly increased the nuclear expression levels of Nrf2. These results indicated that curcumin may protect rat HSCs against oxidative stress and inhibit the GO-induced activation and secretion of ECM molecules in vitro. These effects were mediated by the upregulation of Nrf2 nuclear translocation.

Gastroprotective activities of a polysaccharide from the fruiting bodies of Pleurotus ostreatus in rats.

In this study, a water-soluble polysaccharide (POPw) was successfully purified and identified from the fruiting bodies of Pleurotus ostreatus, with a molecular weight of 2.3×10(4)Da. POPw contained 97.1% total sugar, 0.3% uronic acid and 0.2% protein. Gas chromatography (GC) analysis suggested that POPw was composed of Glc (52.3%), Gal (25.8%), Man (10.0%), Rha (6.1%), and Ara (5.2%). Animal experiments showed that oral administration with POPw significantly inhibited acetic acid-induced gastric lesions in rats, accompanied with a significant increase in mucus synthesis and the prostaglandin production. In addition, POPw could significantly increase the level of glutathione (GSH) and the activity of superoxide dismutase (SOD), as well as decreasing the content of thiobarbituric acid-reactive substances (TBARS) in acetic acid-treated rats with gastric ulcer. These results suggested that the gastroprotective effects of POPw on mice ulcer models can be attributed to its ameliorating effect on oxidative damage and reinforcing effect of gastric mucosal resistance.

Baicalin inhibited nuclear factor κB (NF-κB) activation and attenuated sodium taurocholate of induced experimental pancreatitis in rats

Nuclear factor κB (NF-κB) plays a critical role in development of acute pancreatitis. Baicalin, a root extract of Scutellaria baicalensis Georgi, had protective effects in a rat model of severe acute pancreatitis (SAP). This study investigated the influence of baicalin on pancreatitis and the mechanism of anti-inflammatory effects associated with NF-κB activation. Sixty rats were assigned to four groups (n = 15). SAP rat models were prepared via retrograde injection of 3.5% sodium taurocholate in the pancreatic duct. Sham-treated rats only received open abdomenal surgery. Ten minutes post-surgery, rats were administered 5% baicalin solution or saline. Measures of pancreatic inflammation and pathology were assessed 6 h later. Compared to controls, sodium taurocholate-treated rats had greater pancreatic injury and neutrophil infiltration, stronger activation of lipid peroxidation and oxidative stress, enhanced levels of intercellular adhesion molecule-1 (ICAM-1) and P-selectin, tumor necrosis factor (TNF)-α and IL-6, and decreased IκBα. Baicalin markedly reduced the degree of inflammation and tissue injury, lipid peroxidation, poly (ADP-ribose) and nitrotyrosine production, upregulation/formation of ICAM-1 and P-selectin, neutrophil infiltration, TNF-α and IL-6 production, and increased IκBα in SAP rats. Baicalin attenuated rat pancreatitis induced by sodium taurocholate, and the anti-inflammatory effect was attributed in part to NF-κB inhibition.